Integrating neutrophils, lymphocytes and eosinophils: development and validation of the NLE Index in ICI-treated metastatic melanoma

Prognosis for metastatic melanoma patients treated with immune checkpoint inhibitors (ICIs) remains heterogeneous. Although neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-eosinophil ratio (NER) are established markers, we hypothesized a neutrophil-to-lymphocyte-times-eosinophil (NLE) index would offer superior stratification. We analyzed 194 metastatic melanoma patients receiving ICIs, divided into training ( n = 129) and validation ( n = 65) cohorts. An optimal NLE cutoff categorized patients as NLE-low or NLE-high. Survival outcomes and objective response rate (ORR) were assessed using Kaplan–Meier, Cox regression, and logistic regression. Predictive accuracy of NLE, NLR, and NER was compared. Median overall survival was significantly longer in NLE-low versus NLE-high patients (training: 31.3 versus 6.9 months; P = 0.011; validation: 33.5 versus 9.1 months; P = 0.019). Median progression-free survival also improved significantly in NLE-low patients (training: 10.6 versus 3.1 months; P = 0.029; validation: 13.7 versus 3.9 months; P = 0.012). ORR was higher in NLE-low groups (training: 46.0% versus 13.2%; P < 0.001; validation: 43.6% versus 18.2%; P = 0.078). NLE demonstrated superior predictive accuracy compared with NLR and NER. The NLE index outperforms NLR and NER in predicting survival and response in metastatic melanoma patients treated with ICIs, providing a practical clinical tool.